Obesity-specific G protein coupled receptors

Abstract

Novel obesity-specific G protein-coupled receptors can be used to provide therapeutic reagents for treating obesity and related disorders.

1 . A method of screening for agents which can regulate the activity of an obesity-specific G protein-coupled receptor, comprising the steps of: 
 contacting a test compound with a polypeptide comprising an amino acid sequence which is at least about 50% identical to an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 4; and    detecting binding of the test compound to the polypeptide, wherein a test compound which binds to the polypeptide is identified as a potential therapeutic agent for regulating activity of the obesity-specific G protein-coupled receptor.    
     
     
         2 . The method of  claim 1  wherein the step of contacting is in a cell.  
     
     
         3 . The method of  claim 2  wherein the cell is in vitro.  
     
     
         4 . The method of  claim 1  wherein the step of contacting is in a cell-free system.  
     
     
         5 . The method of  claim 1  wherein the polypeptide comprises a detectable label.  
     
     
         6 . The method of  claim 1  wherein the test compound comprises a detectable label.  
     
     
         7 . The method of  claim 1  wherein the test compound displaces a labeled ligand which is bound to the polypeptide.  
     
     
         8 . The method of  claim 1  wherein the polypeptide is bound to a solid support.  
     
     
         9 . The method of  claim 1  wherein the test compound is bound to a solid support.  
     
     
         10 . A method of screening for agents which regulate a biological activity of an obesity-specific G protein-coupled receptor, comprising the steps of: 
 contacting a test compound with a polypeptide comprising an amino acid sequence which is at least about 50% identical to an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 4; and    detecting a biological activity mediated by the polypeptide, wherein a test compound which increases the biological activity is identified as a potential therapeutic agent for increasing the biological activity of the obesity-specific G protein-coupled receptor, and wherein a test compound which decreases the biological activity of the polypeptide is identified as a potential therapeutic agent for decreasing the biological activity of the obesity-specific G protein-coupled receptor.    
     
     
         11 . The method of  claim 10  wherein the step of contacting is in a cell.  
     
     
         12 . The method of  claim 11  wherein the cell is in vitro.  
     
     
         13 . The method of  claim 10  wherein the step of contacting is in a cell-free system.  
     
     
         14 . The method of  claim 10  wherein the biological activity is cyclic AMP formation.  
     
     
         15 . The method of  claim 10  wherein the biological activity is mobilization of intracellular calcium.  
     
     
         16 . The method of  claim 1  wherein the biological activity is phosphoinositide metabolism.  
     
     
         17 . A method of screening for agents which regulate a biological activity of an obesity-specific G protein-coupled receptor, comprising the steps of: 
 contacting a test compound with a product encoded by a polynucleotide which comprises a nucleotide sequence which is at least about 50% identical to a nucleotide sequence selected from the group consisting of SEQ ID NOS:1 and 3; and    detecting binding of the test compound to the product, wherein a test compound which binds to the product is identified as a potential therapeutic agent for regulating the biological activity of the obesity-specific G protein-coupled receptor.    
     
     
         18 . The method of  claim 17  wherein the product is a polypeptide.  
     
     
         19 . The method of  claim 17  wherein the product is RNA.  
     
     
         20 . A method of reducing a biological activity of an obesity-specific G protein-coupled receptor, comprising the step of: 
 contacting a cell with a reagent which specifically binds to a product encoded by a polynucleotide comprising a nucleotide sequence which is at least about 50% identical to a nucleotide sequence selected from the group consisting of SEQ ID NOS:1 and 3, whereby the biological activity of the obesity-specific G protein-coupled receptor is reduced.    
     
     
         21 . The method of  claim 20  wherein the product is a polypeptide.  
     
     
         22 . The method of  claim 21  wherein the reagent is an antibody.  
     
     
         23 . The method of  claim 20  wherein the product is RNA.  
     
     
         24 . The method of  claim 23  wherein the reagent is an antisense oligonucleotide.  
     
     
         25 . The method of  claim 23  wherein the reagent is a ribozyme.  
     
     
         26 . The method of  claim 20  wherein the cell is in vitro.  
     
     
         27 . The method of  claim 20  wherein the cell is in vivo.  
     
     
         28 . A pharmaceutical composition, comprising: 
 a reagent which specifically binds to a product encoded by a polynucleotide comprising a nucleotide sequence which is at least about 50% identical to a nucleotide sequence selected from the group consisting of SEQ ID NOS:1 and 3; and    a pharmaceutically acceptable carrier.    
     
     
         29 . The pharmaceutical composition of  claim 28  wherein the reagent is an antibody.  
     
     
         30 . The pharmaceutical composition of  claim 28  wherein the reagent is an antisense oligonucleotide.  
     
     
         31 . The pharmaceutical composition of  claim 28  wherein the reagent is a ribozyme.  
     
     
         32 . An isolated and purified polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:1 and 3.  
     
     
         33 . An isolated and purified polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 4.  
     
     
         34 . A preparation of antibodies which specifically bind to a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 4.  
     
     
         35 . The preparation of  claim 34 , wherein the antibodies are monoclonal.  
     
     
         36 . The preparation of  claim 34 , wherein the antibodies are polyclonal.  
     
     
         37 . A method of preparing a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 4, comprising the steps of: 
 culturing a host cell comprising an expression construct encoding the polypeptide under conditions whereby the polypeptide is expressed; and    isolating the polypeptide from the host cell.    
     
     
         38 . A transgenic animal comprising an obesity-specific G protein-coupled receptor.  
     
     
         39 . The transgenic animal of  claim 38 , wherein the obesity-specific G protein-coupled receptor comprises an alteration in its coding sequence.  
     
     
         40 . A host cell comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:1 and 3.  
     
     
         41 . A pharmaceutical composition, comprising: 
 an expression construct encoding a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 4; and    a pharmaceutically acceptable carrier.